Routes of Drug Administration
- Intravenous injection (blood vessels)
- Inhalation
- Subcutaneous injection (epithelium)
- Intramuscular injection (muscle)
General appearance:
- identity, and general elegance is essential for consumer
acceptance, for control of lot-to-lot uniformity and
tablet-to-tablet uniformity
- measurement of size, shape, color, presence or absence
of odor, taste etc
Size and Shape:
- dimensionally described & controlled
- Thickness is only variables
- thickness can be measured by micrometer or by another
device (vernier caliper)
- thickness should be controlled within a ± 5% variation
of standard value
- Round, square, rectangle, capsule, pentagon, oval, etc
Unique identification marking:
- form of embossing, engraving or printing
- include company name or symbol, product code,
product name etc
- Shallow, standard, deep, x-deep, etc.
Pharmacokinetics
The principle of ADME,
A - absorption = how will it get in?
D - distribution = where will it go? (transporters)
M - metabolism = how is it broken down? Effective or
not? (liver - main organ)
E - excretion = how does it leave? (urine, feces)
* blood = carries medication (blood flow), dissolve in your
bloodstream
Drug in solution
Tablet = very limited dissolution
Granules = limited dissolution
Small particles = best dissolution
Organoleptic properties:
- Color distribution must be uniform with no mottling
- For visual color comparison compare the color of
sample against standard color
- presence of odor indicates a stability problem such as
the characteristics odor of acetic acid in an aspirin tablet
- presence of odor could be characteristic of the drug
(Vitamin), added ingredients (flavoring agent) or the
dosage form (film-coated tablet have a characteristic
odor)
- chewable tablet presence or absence of specified taste
can be checked
- tablet level of flaws such as chip, cracks, contamination
from foreign solid substances, surface texture, and
appearance may have zero defect
TABLET COMPRESS MACHINE
A. Single punch tablet compression machine/single
station/ eccentric tablet press machine
- Simplest machine that uses a pair of
punches (upper and lower) and a die
B. Multi punches tablet compression machine/
multi-station/ Rotary presses
Parts of a machine
1. Hopper - contains the granules that are to be compresses
into tablets
Upper punch
- Moves vertically in & out of the die bore
2. Feeder Housing - hopper feeds material into the rotating
die
3. Feed Paddies - helps force feed the granules into dies
during faster rotation
Lower punch
- Remains within the bore of the die
4. Lower cam track - guides the lower pinch during filling
stage so the die bore is overfilled to allow accurate
adjustment
Cam tracks
- Lift and lower both upper and lower punch
5. Depth of Fill (weight control) - adjustable to ensure that
as the punch rises the correct quantity of granule, if
remains within the die, therefore the tablet weight is
correct
6. Fill station - the point where the die has been filled
7. Pre- compression rollers - roller gives granules an initial
compression force to remove excess air that might be
entrapped
8. Main compression rollers - roller apply compression
force to the punches for the final formulation of the
tablet
9. Direction of rotation - varies from machine to machine
10. Ejection cam - guides the lower punch upwards during
tablet ejection
11. Take-off blade - fitted in front of the feeder housing this
deflects the tablet down the discharge chute
Die
- Punch move within the die bore to compress the
granules into tablets
12. Discharge chute - tablet passes through for collection
Quality Control Procedures for Tablets 2. Friability
1. Hardness - Roche friabilator
- amount of strength or hardness and resistance to - plastic chamber that revolves at 25 rpm, dropping
friability to withstand mechanical shakes of the tablets through a Distance of six inches in the
handling in the manufacture, packaging, and friabilator, then operated for 100 revolutions
shipping - compressed tablet that loses less than 0.5 to 1.0 %
- measures the tablet crushing strength of the Tablet weight are considered acceptable
- cracking the tablet between 2nd and 3rd fingers - Performed using uncoated and compressed tablets
with the thumb acting as a fulcrum. If there is a - Expressed in %
sharp snap, the tablet is an acceptable strength - W1 - W2 / W1 x 100
- force required breaking a tablet in a diametric
compression 3. Thickness
- compressed tablet is 5 to 8 kg - Measured using Vernier caliper += 5% of standard
● Monsanto Tester thickness.
- a barrel containing a compressible - Not used for coated tablets
spring held between 2 plungers
- tablet is placed on the lower 4. Disintegration Testing
plunger, and the upper plunger is - determine the compliance with the limits on
lowered onto it Disintegration stated in the individual monographs
● Strong-Cobb Tester except where the label states that the tablets or
- An ad hoc unit of force which is capsules are intended for use as troches, or
a legacy of one of the first tablet chewed, or are designed
hardness testing machines - Whether dosage forms such as tablets, capsules,
- Arbitrary boluses pessaries and suppositories disintegrate
- 1 represented roughly 0.7 within the prescribed time when placed in a liquid
kilogram of force or about 7 medium
newtons - State in which no residue of the unit under test
● Pfizer Tester remains on the screen of the apparatus or not
- compresses tablet between a - 37 degree celsius +- 2
holding anvil and a piston
connected to a force-reading 5. Dissolution Testing
gauge when its plier-like - requirement for all solid oral dosage forms and is
handles are gripped used throughout the development life-cycle for
● Erweka Tester product release and stability testing
- dual-mode: “constant speed” - pivotal analytical test used for detecting physical
and “constant force” changes in an active pharmaceutical ingredient and
- offering accuracy, robust formulated product
design as well as easy and Dissolution - process in which a substance forms a solution
quick handling - measures the extent and rate of solution formation
- operated via a symbol from a dosage form, such as tablet, capsule,
keypad which allows effortless entering of the ointment, etc.
samples number required for testing - important for its bioavailability and therapeutic
● Schleuniger Tester effectiveness
- includes tablet
Hardness Testers , PROBLEMS ENCOUNTERED IN TABLETS
softgel Elasticity SOURCE OF THE PROBLEM,
testers, tablet ● FORMULATION
Disintegration testers, ● COMPRESSION EQUIPMENT
tablet Dissolution ● COMBINATION OF THE TWO.
testers , tablet Friability testers and Tapped
Density testers 1. Capping
- known for their reliability, precision and ease - upper or lower segment of the tablet separates
of use horizontally, during ejection from the tablet press, or
during subsequent handling
2. Lamination
 - separation of the tablet into two or more distinct
granules. and add proper amount of binder.
layers ➢ Tablets expand. ➢ Improve granulation. Add dry
Detection of these problems: subjecting tablets to friability ➢ Granulation too binders.
test cold. ➢ Compress at room temperature.
Causes Remedies Machine (Dies, Punches And Tablet Press)

- air is entrapped among - Relative compressibility Causes Remedies

the particles or granules of various materials
➢ Tablet expands on ejection due ➢ Use a tapered die.
and does not escape until may be reflected by
to air entrapment ➢ Use special
the compression their degree of
➢ Deep concavities cause cracking take-off
pressure is released consolidation (crown
while removing tablets
- due to the deformational thickness) when
properties of the compressed in standard
formulation during and tooling under identical 5. Sticking
immediately following compression conditions - the tablet material adhering to the die wall
compression - Improperly dried or improperly lubricated granules
Formulation (Granulation)
3. Chipping
Causes Remedies
- breaking of the tablet edges, while the tablet leaves
the press of during the subsequent handling and ➢ Granules not ➢ Dry the granules properly. Make
coating operations dried properly. moisture analysis to determine
- due to the incorrect equipment setting, misaligned ➢ Too little or limits.
ejection improper ➢ Increase or change lubricant.
lubrication ➢ Reduce the amount of binder or
Formulation (Granulation)
➢ Too much binder use a different type of binder.
Causes Remedies ➢ Hygroscopic ➢ Modify granulation and
granular material. compress under controlled
➢ Sticking on punch ➢ Dry the granules properly or ➢ Oily or way humidity.
faces increase lubrication. materials ➢ Modify mixing process. Add an
➢ Too dry granules ➢ Moisten the granules to ➢ Too soft or weak absorbent.
➢ Too much binding plasticize. Add hygroscopic granules. ➢ Optimize the amount of binder
causes chipping at subs. and granulation technique.
bottom. ➢ Optimize binding, or use dry
Machine (Dies, Punches And Tablet Press)
binders
Tablet Presses (Dies, Punches And Tablet Press) Causes Remedies

Causes Remedies ➢ Concavity too deep for ➢ Reduce concavity to

granulation. optimum
➢ Groove of die worn at ➢ Polish to open end, ➢ Too little pressure. ➢ Increase pressure.
compression point. reverse or replace the die. ➢ Compressing too fast ➢ Reduce speed.
➢ Barreled die (center of ➢ Polish the die to make it
the die wider than cylindrical.
ends). ➢ Polish the punch edges 6. Picking
➢ Edge of punch face ➢ Reduce concavity of - when small amount of material from a tablet is
turned inside/inward. punch faces. Use flat sticking to and being removed off from the
➢ Concavity too deep to punches. tablet-surface by a punch face
compress properly - more prevalent on the upper punch faces
- improperly dried
4. Cracking - punch tips have engraving or embossing letters, as
- Small, fine cracks observed on the upper and lower well as the granular material is improperly dried
central surface of the tablets, or very rarely on the Formulation (Granulation)
sidewall are referred to as ‘Cracks’ Causes Remedies
Formulation (Granulation)
➢ Excessive moisture in ➢ Dry properly the granules,
Causes Remedies
granules. determine optimum limit.
➢ Large size of ➢ Reduce granule size. Add fines. ➢ Too little or improper ➢ Increase lubrication; use
granules. II. lubrication colloidal silica as a polishing
➢ Too dry ➢ Moisten the granules properly ➢ Low melting point agent‘, so that material does
substances, may not cling to punch faces.
 soften from the heat ➢ Add high melting-point little clearance ➢ Rework to proper size.
of compression and materials. Use high melting ➢ Too much pressure in Increase clearance.
lead to picking point lubricants. the tablet press ➢ Reduce pressure. Or Modify
➢ Low melting point ➢ Refrigerate granules and the granulation
medicament in high entire tablet press.
concentration. ➢ Compress at room
➢ Too warm granules temperature. Cool sufficiently 9. Double impression
when compressing. before compression. - Involves only dose punches, which have a monogram
➢ Too much binder. ➢ Reduce the amount of binder, or other engraving on them
change the type or use dry
Causes Remedies
binders.
Machine (Dies, Punches And Tablet Press) ➢ Free rotation of ➢ Use keying in tooling, i.e. insert
either upper a key alongside of the punch, so
Causes Remedies punch or lower that it fits the punch and
punch during prevents punch rotation.
➢ Rough or ➢ Polish faces to high luster.
ejection of a ➢ Newer presses have anti-turning
scratched punch ➢ Design lettering as large as
tablet devices, which prevent punch
faces possible.
rotation
➢ Bevels or dividing ➢ Plate the punch faces with
lines too deep. chromium to produce a smooth
➢ Pressure applied is and non-adherent face. PROBLEMS IN TABLET COATING AND
not enough; too ➢ Reduce depths and sharpness. CORRESPONDING REMEDIES
soft tablets ➢ Increase pressure to optimum
1. Blistering
7. Filming - local detachment of film from the substrate forming
- slow form of sticking and is largely due to excess blister
moisture in the granulation
Reason Cause Remedies

8. Binding Entrapment of gases in or Effect of Use mild

- when the tablet adhere, sieze or tear in the die. underneath the film due temperature on the drying
- A film is formed in the die and ejection of the tablet is to overheating either strength, elasticity conditions
hindered. With excessive binding, the tablet sized are during spraying or at the and adhesion of .
end of the coating run the film
cracked and it may crumble apart
Formulation (Granulation)
2. Chipping
Causes Remedies
- defect where the film becomes chipped and dented ,
➢ Too moist granules and ➢ Dry the granules properly. usually at the edges of the tablet
extrudes around the ➢ Increase the amount of - Reason: Incorrect machine settings, specially mis-set
lower punch. lubricant or use a more ejection take-off.
➢ Insufficient or improper effective lubricant.
lubricant ➢ Reduce granular size, add 3. Cratering
➢ Too coarse granules. more fines, and increase the
- defect of film coating whereby volcanic-like craters
➢ Too hard granules for quantity of lubricant.
the lubricant to be ➢ Modify granulation. appears exposing the tablet surface
effective. Reduce granular size. Reason Causes Remedies
➢ Granular material is ➢ If coarse granules, reduce
very abrasive and its size. The coating sol. Inefficient Use efficient and
cutting into dies. ➢ Use wear-resistant dies penetrates the surface, drying. optimum drying
➢ Granular material is too ➢ Reduce temperature. often at the crown conditions.
warm. ➢ Increase clearance if it is where the surface is Higher rate
➢ sticks to the die extruding. more porous, causing of application Increase viscosity
Machine (Dies, Punches And Tablet Press) localized of coating of coating solution
disintegration of the solution. to decrease spray
Causes Remedies core and disruption of application rate.
the coating
➢ Poorly finished dies ➢ Polish the dies properly
➢ Rough dies due to ➢ Investigate other steels or
abrasion, corrosion. other materials or modify
➢ Undersized dies. Too granulation.
4. Picking
- defect where isolated areas of film are pulled away
from the surface when the tablet sticks together and
then part
Sticking and picking reasons:
- Over wetting or excessive film thickness causes to
stick each other or to coating pan
- On drying, a piece of film may remain adhered to the
pan
Reasons Causes Remedies

similar to cratering Inefficient Use optimum and

that produces an drying. efficient drying
overly wet tablet conditions or increase
bed where Higher rate the inlet air temp..
adjacent tablets of Decrease the rate of
can stick together application application of coating
and then break of coating sol. by increasing
apart solution viscosity of coating sol.

5. Pitting
- defect whereby pits occur in the surface of
the tablet core without any visible
disruption of the film coating

6. Blooming
- defect where coating becomes dull
immediately or after prolonged storage at
temperature

7. Blushing
- defect is best described as whitish specks or
haziness in the film

8. Colour variation
- a defect which involves variation in colour
of the film

9. Infilling
- defect that renders the intagliations
indistinctness

10. Orange peel or roughness

- Is surface defect resulting in the film being
rough and non glossy. Appearance is
similar to an orange.

11. cracking/spitting
- defect in which the film either cracks
across the crown of the tablet (cracking) or
splits around the edges of the tablet
(Splitting)